Treatment of hepatitis C has been disappointing with less than one-third achieving a sustained response and most experiencing significant side effects. Although Interferon is the only FDA approved drug for the treatment of hepatitis C in adults, it is not approved for children. A pilot trial was conducted at Pennsylvania State University, College of Medicine in which adult patients with hepatitis C who had failed to respond to interferon were treated with amantadine-HC1 for six months. Serum alanine aminotransferase values decreased in 64 percent of the patients with amantadine therapy compared to intervals without therapy or to interferon therapy. Twenty-seven percent of patient treated with amantadine had normalization of ALT values and loss of hepatitis C virus RNA. Promising results of the pilot study are reason for further investigation. This grant hypothesizes that administration of amantadine-HC1 to patients with chronic hepatitis C will inhibit hepatic inflammation by repressing replication of the hepatitis C virus. We propose to investigate this hypothesis by conducting a prospective randomized double-blind placebo-controlled trial in 100 adult and 50 pediatric patients with chronic hepatitis C. The following specific aims are proposed: 1) Evaluate the efficacy of amantadine as an active antiviral agent for hepatitis C in adult patients who had previously failed therapy with interferon, 2) Study the safety and efficacy of amantadine in children with hepatitis C infection, 3) Evaluate the effects of amantadine on hepatic inflammation and hepatitis C RNA blood levels in naive patients who either decline from interferon therapy or who cannot take interferon for medical reasons, 4) Study response rate and durability of response in patients treated with six versus 12 months of amantadine, and 5) elucidate be effects of amantadine therapy on the patient's quality of lift. These studies are part of one long term goals towards understanding the mechanisms involved in infection and treatment of the hepatitis C virus.